KR102195348B1 - 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 - Google Patents

단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 Download PDF

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Publication number: KR102195348B1
Authority: KR; South Korea
Prior art keywords: alkyl; indol; pyridin; cyano; haloalkyl
Prior art date: 2018-11-15

Application number

KR1020180140578A

Other languages

English (en)

Korean (ko)

Other versions

KR20200056652A (ko

Inventor

박지연

김승찬

기소영

심예리

Original Assignee

에이치케이이노엔 주식회사

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2018-11-15

Filing date

2018-11-15

Publication date

2020-12-24

2018-11-15 Priority to KR1020180140578A priority Critical patent/KR102195348B1/ko

2018-11-15 Application filed by 에이치케이이노엔 주식회사 filed Critical 에이치케이이노엔 주식회사

2019-11-14 Priority to EP19885184.2A priority patent/EP3880671A4/fr

2019-11-14 Priority to US17/294,226 priority patent/US20220009902A1/en

2019-11-14 Priority to CA3120055A priority patent/CA3120055C/fr

2019-11-14 Priority to JP2021526602A priority patent/JP7312823B2/ja

2019-11-14 Priority to CN201980075052.6A priority patent/CN113166094A/zh

2019-11-14 Priority to PCT/KR2019/015516 priority patent/WO2020101382A1/fr

2019-11-14 Priority to AU2019381113A priority patent/AU2019381113B2/en

2019-11-14 Priority to MX2021005740A priority patent/MX2021005740A/es

2019-11-14 Priority to BR112021009486-5A priority patent/BR112021009486A2/pt

2020-05-25 Publication of KR20200056652A publication Critical patent/KR20200056652A/ko

2020-12-24 Application granted granted Critical

2020-12-24 Publication of KR102195348B1 publication Critical patent/KR102195348B1/ko

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150000001875 compounds Chemical class 0.000 title claims abstract description 84
239000008194 pharmaceutical composition Substances 0.000 title description 4
229940043355 kinase inhibitor Drugs 0.000 title description 3
239000003909 protein kinase inhibitor Substances 0.000 title description 3
150000003839 salts Chemical class 0.000 claims abstract description 17
238000011282 treatment Methods 0.000 claims abstract description 8
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 7
230000002265 prevention Effects 0.000 claims abstract description 6
206010028980 Neoplasm Diseases 0.000 claims abstract description 5
201000011510 cancer Diseases 0.000 claims abstract description 5
125000000217 alkyl group Chemical group 0.000 claims description 100
229910052799 carbon Inorganic materials 0.000 claims description 52
229910052739 hydrogen Inorganic materials 0.000 claims description 47
125000003118 aryl group Chemical group 0.000 claims description 43
125000004093 cyano group Chemical group *C#N 0.000 claims description 42
125000001072 heteroaryl group Chemical group 0.000 claims description 40
125000006642 (C1-C6) cyanoalkyl group Chemical group 0.000 claims description 38
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 36
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 25
125000003342 alkenyl group Chemical group 0.000 claims description 24
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 20
150000002367 halogens Chemical class 0.000 claims description 19
238000000034 method Methods 0.000 claims description 17
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 13
125000001188 haloalkyl group Chemical group 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
239000000126 substance Substances 0.000 claims description 7
125000004001 thioalkyl group Chemical group 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 3
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201000010099 disease Diseases 0.000 abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
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208000012902 Nervous system disease Diseases 0.000 abstract description 4
208000025966 Neurological disease Diseases 0.000 abstract description 4
208000015181 infectious disease Diseases 0.000 abstract description 4
208000030159 metabolic disease Diseases 0.000 abstract description 4
208000016097 disease of metabolism Diseases 0.000 abstract 1
230000015572 biosynthetic process Effects 0.000 description 71
238000003786 synthesis reaction Methods 0.000 description 71
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238000006243 chemical reaction Methods 0.000 description 17
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 13
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238000004440 column chromatography Methods 0.000 description 7
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239000003153 chemical reaction reagent Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
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238000002360 preparation method Methods 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
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125000005843 halogen group Chemical group 0.000 description 4
239000000463 material Substances 0.000 description 4
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239000007787 solid Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
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KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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239000012153 distilled water Substances 0.000 description 3
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239000000376 reactant Substances 0.000 description 3
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229910000104 sodium hydride Inorganic materials 0.000 description 3
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
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CCLIDYYBSSRFFY-UHFFFAOYSA-N N-[3-[2-(cyclopropanecarbonylamino)pyridin-4-yl]-1H-indol-7-yl]cyclohexanecarboxamide Chemical compound C1(CC1)C(=O)NC1=NC=CC(=C1)C1=CNC2=C(C=CC=C12)NC(=O)C1CCCCC1 CCLIDYYBSSRFFY-UHFFFAOYSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Immunology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Transplantation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

KR1020180140578A 2018-11-15 2018-11-15 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 KR102195348B1 (ko)

Priority Applications (10)

Application Number	Priority Date	Filing Date	Title
KR1020180140578A KR102195348B1 (ko)	2018-11-15	2018-11-15	단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물
US17/294,226 US20220009902A1 (en)	2018-11-15	2019-11-14	Novel compound as protein kinase inhibitor, and pharmaceutical composition comprising thereof
CA3120055A CA3120055C (fr)	2018-11-15	2019-11-14	Nouveau compose utilise en tant qu'inhibiteur de proteine kinase, et composition pharmaceutique le comprenant
JP2021526602A JP7312823B2 (ja)	2018-11-15	2019-11-14	タンパク質キナーゼ阻害剤としての新規化合物およびそれを含む薬学的組成物
EP19885184.2A EP3880671A4 (fr)	2018-11-15	2019-11-14	Nouveau composé utilisé en tant qu'inhibiteur de protéine kinase, et composition pharmaceutique le comprenant
CN201980075052.6A CN113166094A (zh)	2018-11-15	2019-11-14	作为蛋白激酶抑制剂的新型化合物和包含其的药物组合物
PCT/KR2019/015516 WO2020101382A1 (fr)	2018-11-15	2019-11-14	Nouveau composé utilisé en tant qu'inhibiteur de protéine kinase, et composition pharmaceutique le comprenant
AU2019381113A AU2019381113B2 (en)	2018-11-15	2019-11-14	Novel compound as protein kinase inhibitor, and pharmaceutical composition comprising thereof
MX2021005740A MX2021005740A (es)	2018-11-15	2019-11-14	Novedoso compuesto como inhibidor de proteina quinasa, y composicion farmaceutica que comprende el mismo.
BR112021009486-5A BR112021009486A2 (pt)	2018-11-15	2019-11-14	composto como inibidor de proteína quinase e uso do mesmo, composição farmacêutica e método para prevenir ou tratar doenças relacionadas à proteína quinase

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
KR1020180140578A KR102195348B1 (ko)	2018-11-15	2018-11-15	단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물

Publications (2)

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KR20200056652A KR20200056652A (ko)	2020-05-25
KR102195348B1 true KR102195348B1 (ko)	2020-12-24

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KR1020180140578A KR102195348B1 (ko)	2018-11-15	2018-11-15	단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물

Country Status (10)

Country	Link
US (1)	US20220009902A1 (fr)
EP (1)	EP3880671A4 (fr)
JP (1)	JP7312823B2 (fr)
KR (1)	KR102195348B1 (fr)
CN (1)	CN113166094A (fr)
AU (1)	AU2019381113B2 (fr)
BR (1)	BR112021009486A2 (fr)
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AU2019381113A1 (en)	2021-07-01
AU2019381113B2 (en)	2022-07-28
JP2022508128A (ja)	2022-01-19
MX2021005740A (es)	2021-08-11
KR20200056652A (ko)	2020-05-25
EP3880671A4 (fr)	2022-07-27
EP3880671A1 (fr)	2021-09-22
CN113166094A (zh)	2021-07-23
CA3120055C (fr)	2023-09-26
JP7312823B2 (ja)	2023-07-21
WO2020101382A1 (fr)	2020-05-22
CA3120055A1 (fr)	2020-05-22
BR112021009486A2 (pt)	2021-08-10

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